This invention relates to an article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances, said wall being made using a biodegradable polymeric material permeable to the active substance.
For the controlled delivery of active substances articles have been developed showing a great diversity in shape, sizes and other properties capable of affecting the rate of delivery of an active substance from the usability of the article. Particularly the selection of the material of which the article is made can largely affect the final possibilities of using the article. On the basis of the nature of the materials used, which are often polymeric materials, it is possible to divide the articles for the controlled delivery, which, among other things, are intended for use in man and animal, into two groups. On the one hand, there are the articles made of materials that cannot be broken down in the body. After the active substance has been delivered, the article must be removed, which may be regarded as a drawback. On the other hand, there are the articles on the basis of (bio) degradable materials. When the active substance has been delivered in full or in part, a breakdown of the article into components innocuous to the organism occurs so that removal of the article is no longer necessary.
"Hydrogels and Biodegradable Polymers for the Controlled Delivery of Drugs" by N. B. Graham and D. A. Wood in Polymer News, 1982, Vol. 8, pages 230-236, discloses all kinds of delivery systems of the basis of biodegradable polymer substrates charged with active substance, which polymer substrates, among other things, can be subdermally applied to man and animal. Such delivery systems may have the form of e.g., spherical particles. These particles consist of biodegradable matrices surrounding the active substance. Such a delivery system, however, has the drawback that the particles can hardly, if at all, be surgically removed should the active substance would not be accepted. The same drawback is connected with other delivery systems referred to in this article, such as microcapsules having an average size of 5 to 50 .mu.m. The above article by N. B. Graham and D. A. Wood further mentions films as delivery system. Such films, however, have the drawback that a subdermal use thereof requires surgery, which is considered laborious and may also involve certain risks.
The usability of an article is not exclusively determined by the possibility of breakdown of the article after delivery of the active substance. Also the possibilities of a proper control of the rate of delivery of the active substance are important when designing an article. Because in many cases the active substance will be released by a diffusion process, the material selection may again be a decisive factor for the delivery properties finally obtained by the article. Besides, it is also possible to affect the delivery properties by varying the shape and sizes of the article.
"Sustained Drug Delivery System II: Factors Affecting Release Rates from poly-.epsilon.-caprolactone and Related Biodegradable Polyesters" by C. G. Pitt et al in J. Pharm. Sc., Vol. 68, No. 12, 1979, pages 1534-1538, discloses films on the basis of homo--and copolymers of .epsilon.-caprolactone, DL-lactic acid and glycolic acid. With regard to the microcapsules on the basis of poly-.epsilon.-caprolactone described in this article and in U.S. Pat. No. 4,148,871 of C. G. Pitt et al (1986) it is particularly advanced that these are prepared by melt extrusion, after which the ends of the resulting hollow tube are closed after filling with the medicine. These microcapsules, however, have the drawback that the rate of delivery of the medicine per unit of area, which is adjustable by varying the wall thickness of the hollow tube, can only be changed to a very limited extent, e.g., by a factor of 2 to 3.
For the delivery of active substances having a high molecular weight, European Patent Application No. 86402527.5 (Porous bioadsorbable polyesters, 1986) of A. Schindler describes the development of a porous degradable fibre made of polymer.
"Controlled Release Technologies: Methods, Theory and Applications" Vol II by A. F. Kydonieus, page 165 ff , CRC Press, Inc., discloses the use of hollow fibers for the delivery of insect pheromones. Further, "Hollow Fibers as an Oral Sustained-Release Delivery System" by M. A. Hussain et al in Pharm. Res., Vol. 6, No. 1, 1989, pages 49-52, describes the delivery of Phenyl Propanolamine (PPA) from hollow fibers. As indicated, however, such hollow fibers are open on one side so that they are unsuitable for the controlled delivery of medicines in a subdermal or other use in man and animal.